Graduate Education:

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Medical Education:

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Neurological and psychiatric illnesses affect more than 50 million Americans annually, and up to one billion people around the world. These numbers underscore the importance of advancing our understanding of the human brain in health and disease.

My laboratory’s focus is synaptic transmission and mapping synaptic networks involved in fear, learning and sleep regulation. Pharmacological, physiological, and microscopic studies have made seminal contributions to our field, however the intracellular mechanisms that regulate neurotransmission remained mostly unknown until recently. Prior to becoming an EVMS faculty, I worked in the laboratory of T. C. Südhof, Nobel Prize in Medicine, 2013, to investigate the molecular mechanisms of neurotransmitter release. We have demonstrated that SNARE protein assembly-disassembly is dynamic, and that it is regulated by protein kinase C for many neurotransmitter types.

Assembly of a tripartite core complex from three SNARE protein is required for synaptic vesicle fusion. Our findings support the idea that core complex assembly represents an important point of regulation in neurotransmitter secretion and that presynaptic plasticity can operate at the step of prefusion by regulating the size of the readily releasable pool. In another series of studies, we found that Rab3 interacting molecule 1 alpha (RIM1α) is a target for protein kinase A. As an independent investigator, I extended these studies to downstream effectors of phospho-RIM1α and to another kinase, ERK, a kinase that is also important for presynaptic plasticity, likely mechanism of learning and memory.

To evaluate the role of synaptic mechanisms in learning and memory we have adopted/developed behavioral techniques and collaborated with Dr. Sanford’s sleep laboratory to assess the connection of these mechanisms to sleep. We have also successfully collaborated with Dr. Britten’s lab to evaluate radiation induced changes in neurotransmission and cognitive performance. Recent additions to our technical arsenal are the CLARITY technique (see image), allowing the imaging of intact brains, and optogenetics, that facilitates functional and microscopic mapping of neuronal networks.

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Courses Taught:

Medical courses:

Histology (Course director)

Neuroscience

Organ System Function

Graduate courses:

Concepts in Research Design (Course director)

Essentials of Physiology

Advanced Cell Biology

Cell Structure and Function

Current Projects:

Ongoing Research Support

NIMH Lonart & Sanford (MPI) 9/6/2014 to 8/30/2016

Title: Role of amygdalar inputs to locus coeruleus in sleep regulation.

Role: Principal Investigator.

NIMH L.D. Sanford (PI) 9/26/2013 to 7/31/2018

Title: Limbic modulation of stress-induced alterations in sleep.

Role Co-Inv.

NASA R.A. Britten (PI) 2/27/2014 to 2/26/2018

Title: Changes in Neuroproteome Associated with HZE-induced Impairment of Cognition